Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tear fluid plasmin activities were measured by a fluorometric assay based on a lyophilized kit with the 7-amido-4-trifluoromethylcoumarin derivative of the tripeptidyl H-D-Val-Leu-Lys as substrate. The rapid, sensitive method can detect proteolytic activity in small volume tear fluid samples. Plasmin activity levels (IU/L) measured from the samples were corrected with tear fluid flows (microliters/min), yielding a parameter called plasmin flux (microIU/min). Correction is important when patients show tearing due to irritation. Tear fluid samples were collected from 32 asymptomatic contact lens (CL) wearers and 27 controls. Plasmin activity values (2.7 +/- 0.3 IU/L) of CL wearers were higher (p < 0.00006) than those of the controls (1.6-0.1). Mean plasmin flow was 12.6 +/- 1.5 microliters/min for CL wearers and higher for controls (6.8 +/- 0.5 microliters/min). The difference was not significant (p = 0.063). Plasmin flux values of CL wearers (30.0 +/- 4.1 microIU/min) were conspicuously higher than those of controls (10.2 +/- 0.7 microIU/min, p < 0.00006). We conclude that elevated tear fluid proteolytic activity may be related to pathological changes associated with CL wear.
Cornea 1994 May
PMID:Elevation of tear fluid plasmin activity of contact lens wearers studied with a rapid fluorometric assay. 803 69

Cytochalasins B (CB), dihydroB (H2CB), and D (CD) were found to cause loss of fibronectin (Fn) from the cell surface of normal rabbit corneal fibroblasts, breakdown of F-actin-containing microfilament bundles ("stress fibers"), and increase levels of type I interstitial collagenase (MMP-1) in the medium. In contrast to the effects of plasmin, the cytochalasins caused withdrawal of cells from the Fn mesh but not total loss of the mesh, and the collagenase was essentially all in latent form. The results are consistent with the possibility that cytochalasins, like plasmin, perturb the alpha 5 beta 1 integrin (Fn) receptor. Unlike plasmin, which degrades Fn to result in such a perturbation, however, the cytochalasins are thought to do so by directly disrupting cytoplasmic F-actin microfilaments associated with focal contact adhesive structures, to result in changes in the Fn receptor that cause loss of Fn. Thus, plasmin acting extracellularly and cytochalasins acting intracellularly are both thought to be able to modulate the secretion (and possibly also the synthesis) of MMP-1 by corneal fibroblasts by perturbing the Fn receptor located in the focal contact. The presence of all active collagenase after treatment with plasmin, as opposed to latent collagenase after treatment with cytochalasin, supports the interpretation that the events of secretion and activation of collagenase can be uncoupled.
Cornea 1994 Jan
PMID:Regulation of corneal fibroblast MMP-1 secretion by cytochalasins. 813 7

A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume tear fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by tear fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.
Cornea 1994 Mar
PMID:A rapid fluorometric assay for tear fluid plasmin activity. 815 87

Plasmin was found to degrade the fibronectin (Fn) mesh produced by cultures of normal rabbit corneal fibroblasts, cause breakdown of F-actin-containing microfilament bundles ("stress fibers"), and increase levels of active type I interstitial collagenase (MMP-1) in the medium. Fibroblast cultures derived from alkali-burned, ulcerating rabbit corneas also responded to plasmin by secreting collagenase, detected only in active form. Moreover, harvests from organ cultures of ulcerating corneas not only had higher levels of urokinase-like plasminogen activator (uPA) than normal cultures but also had higher levels of Fn degradation fragments. The results are consistent with reports that indicate that perturbation of the alpha 5 beta 1 integrin (Fn) receptor by proteolytic fragments of Fn causes the increased synthesis and secretion of MMP-1. The uPA/plasmin system, therefore, might have an important role in regulating collagenase synthesis, secretion, and activation during wound remodelling and stromal ulceration.
Cornea 1993 Sep
PMID:Regulation of corneal fibroblast MMP-1 collagenase secretion by plasmin. 830 64

The avascular cornea has limited access to plasma proteins, including plasminogen, a protein that is synthesized by the liver and supplied to most tissues via the blood. Recent experiments by others using plasminogen-deficient mice revealed the importance of plasmin, the active form of plasminogen, for the maintenance of the normal cornea and for corneal wound healing [Kao, Kao, Bugge, Kaufman, Kombrinck, Converse, Good and Degan (1998) Invest. Ophthalmol. Vis. Sci. 39, 502-508; Drew, Kaufman, Kombrinck, Danton, Daugherty, Degen and Bugge (1998) Blood 91, 1616-1624]. In the present experiments, plasmin was identified as a major serine proteinase in the human cornea. The major plasminogen and plasmin forms on non-reducing zymograms and Western blots had Mr values of 76x10(3) and 85x10(3), with minor forms of Mr 200x10(3), 135x10(3), 68x10(3) and 45x10(3). Angiostatin-like peptides with Mrs of 48x10(3), 45x10(3) and 38x10(3) were observed which bound to lysine-Sepharose and reacted with anti-plasminogen monoclonal antibodies directed towards kringle domains 1-3 of plasminogen. The cornea contained 1.1+/-0.15 microgram of plasminogen+plasmin/cornea, or 0.54+/-0.05 microgram of plasminogen+plasmin/mg of protein. Cornea conditioned medium contained nine times the amount of plasminogen+plasmin that could be extracted from the cornea. These data suggested that corneal cells, unlike most extrahepatic cells, synthesize plasminogen. The synthesis of plasminogen by the cornea was confirmed by immunoprecipitation of metabolically labelled plasminogen, sequencing of its cDNA obtained by reverse transcriptase-PCR and inhibition of protein synthesis. Interleukins-1alpha and -1beta stimulated corneal plasminogen synthesis 2-3-fold; however, interleukin-6 decreased corneal plasminogen synthesis by approx. 40% at early times after addition of the cytokine. By 24 h of culture, no differences were noted in the presence and absence of interleukin-6. Thus the cornea can synthesize plasminogen and regulate its synthesis in response to its environment, including cytokines induced in the cornea by injury and inflammation. Therefore the cornea can control the amount of plasminogen, the precursor of both plasmin and angiostatin.
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PMID:Extrahepatic synthesis of plasminogen in the human cornea is up-regulated by interleukins-1alpha and -1beta. 1021 10

Keratocytes, corneal resident cells in the corneal stroma, exist between collagen lamellae and maintain the corneal stromal structure. When the corneal stroma is damaged, keratocytes are transformed to myofibroblasts to aid corneal wound healing by phagocytizing debris. Keratocytes and extracellular collagen influence each other because keratocytes cultured in a 3D collagen gel undergo morphological changes and keratocytes produce metalloproteases that degrade extracellular collagen. IL-1 and plasminogen are critical mediators for collagen degradation. The plasminogen system contributes to tissue repair by activating matrix metalloproteinases (MMPs), releasing growth factors from the extracellular matrix and extracellular matrix degradation. Urokinase-type plasminogen activator (uPA) is thought to be involved in corneal disorders and regulates corneal wound healing. uPA is a serine protease synthesized by various cells such as corneal epithelial cells, corneal fibroblasts, vascular endothelial cells, smooth muscle cells, monocytes, macrophages, and malignant tumor cells of different origins. Here, we review the role of uPA in corneal stromal wound healing. uPA is expressed in leukocytes and corneal fibroblasts in the corneas of patients with corneal ulcerations suggesting it is a key regulator of corneal stromal wound healing. uPA is directly involved in plasmin-mediated collagen degradation induced by IL-1. Moreover, uPA is critically involved in promoting leukocyte infiltration in corneal inflammation by activating MMP-9. This activation is presumably directly and indirectly mediated by the plasminogen/plasmin cascade. Moreover, uPA mediates the release of inflammatory cytokines from corneal fibroblasts to promote leukocyte infiltration.
Cornea 2016 Nov
PMID:Regulatory Mechanism of Collagen Degradation by Keratocytes and Corneal Inflammation: The Role of Urokinase-Type Plasminogen Activator. 2766 Oct 72